Currently there is no proven effective treatment to decrease brain mercury levels. Although chelators in combination with various other medicinal agents have been prescribed there is no objective evidence that these treatments are effective. Some drug combinations may in fact increase brain levels by causing a re-distribution of tissue stores. The aim of this study is to determine if brain mercury levels can be reduced by therapeutic treatment with 2,3-dimercaptopropane-1-sulphonate (DMPS), alone and in combination with other agents often prescribed to help eliminate Hg. Experiments were conducted to examine the effects of various combinations of DMPS, ascorbate (ASC) and glutathione (GSH) on mercury levels in the brain. Rats were exposed 2 hours/day for 10 days to 4 mg/m3 mercury vapor. This exposure regimen has been found to result in relatively high levels of mercury in the brain with no obvious neurotoxicity. The rats were removed from the exposure for 7 days to allow the Hg levels to reach equilibrium in the brain. Animals were then treated with DMPS, GSH, or ASC alone, or in various combinations for one week. Initial data indicate that DMPS caused a more rapid elimination of Hg from the brains of exposed rats. GSH and ASC alone or in combination did not appear to increase the efficacy of DMPS. Additional studies were conducted to evaluate the effects of lipoic acid, and insulin in combination with DMSA on elimination of Hg from the brain and kidney of exposed rats. Lipoic acid has been prescribed for autistic children to theoretically remove brain mercury, although there are no data to support this effect. Insulin has been reported to facilitate the transfer of drugs across the blood-brain barrier, and may also facilitate the transfer of free and bound Hg out of the cells. Neither of these compounds improved the efficacy of DMSA in depleting brain Hg.